Neutrophil-Elastase Inhibitor- Sivelestat Assists in Reducing Ischemia Reperfusion Injury in a Muscle Flap Model: An Experimental Study
Zeynep Kamuran Sevim, Memet Yazar, Aköz Funda Saydam, Volkan Medeni Kıyak, Aysin Yeşilada Karasoy, Sami Samin, Şenay Yener, Dilgem Memmedov, Başak Erginel and Fatih A. Aydın
World Journal of Surgical Research 2013, 2:10
To examine the effectiveness of a neutrophil elastase inhibitor, Sivelestat on ameliorating ischemia reperfusion injury in a muscle flap model.
Materials and Method
Eighteen male, 8-week old, specific pathogen-free Sprague Dawley rats were examined in 3 groups; Saline-treated control group(CG)(n=6), Ischemia group (IG)(n=6), Sivelestat-treated group(SG)(n=6). Gastrocnemius muscle flap was approached as previously described in studies. The sural artery branching from the politeal artery was clamped with 2v microvascular clamps. In the control group, the clamps were left in place for 5 hours of ischemia, prosecuted by 3 hours of reperfusion and saline was given during the reperfusion period.In the ischemia group, the gastrocnemius muscle flap was raised and islanded and the vascular pedicle was tied to mimic total ischemia. In Sivelestat group, the gastrocnemius muscle flap was raised as an islanded flap, the pedicle was clamped with 2v microvascular clapms for 5 hours, prosecuted by 3 hours of reperfusion. During the reperfusion period, a 16 gauge cannula was placed from the tail veins of the rats and Sivelestat was infused at a 10 mg/kg/hour dosage for 3 hours creating a pharmacological postconditioning procedure.After a total of 8 hours, the incisions were sutured and the rats in all groups were examined for 7 days in terms of wound healing, allergic reactions and general conditions. On the seventh day of reperfusion, gastrocnemius muscles were harvested for histological analysis with hematoxylene eozine and for myeloperoxidase activity and formeasuring the amount ofbicinchoninic acid which are both predictors of neutrophil elastase accumulation in the tissues.
Inflammatory reaction in groups 1 and 2 were predominated by lymphocytes, followed by eosinophil leukocytes and plasmocytes resulting in edema collection. In group 3, the sivelestat-treated rats, the number of neutrophil leukocytes are much less, the inflammatory reaction is attenuated with less edema collection in between the tissues.Median tissue myeloperoxidase levels were significantly elevated in control muscle(group1) 2.45 (1.32-4.28) units /g wet weight) compared with that harvested from ischemic 1.12 (1.08-2.02) (p<0.001).
Use of Sivelestat will aid in decreasing the degree of myozite damage in upper limb replantations, crush syndromes and compartment syndromes and will help obtain more functional results in hand surgery where warm ischemia time is of utmost importance.
Neutrophil elastase inhibition, ischemia reperfusion injury, Sivelestat, limb replantation